Investigation of the anti-fibrotic action of the NCE T03 in comparison to Pirfenidone in A549 cells.

<bold>Introduction:</bold> IPF is a fibrotic disease of the respiratory tract characterized by chronic inflammation and tissue remodeling resulting in fibrosis. Epithelial cells secrete pro-inflammatory cytokines, when damaged, causing further inflammatory responses from invading immune cells. This generates a self-perpetuating cycle promoting the development of fibrotic tissue. TGFβ is the major pro-fibrotic factor which triggers extracellular matrix (ECM) accumulation and the transformation of epithelial cells to myofibroblasts (EMT). <bold>Aim:</bold> The anti-fibrotic actions of T03 were investigated in a well-established fibrosis model in the lung epithelial A549 cell line as well as human primary lung fibroblasts (HPF). The efficacy of T03 was compared to one standard of care, Pirfenidone. <bold>Methods:</bold> A549 cells and HPF were stimulated with TGFβ to induce fibrosis. Pro-collagen 1 and HSP47 expression was quantified by Western Blot and immunocytochemistry (ICC). In addition, pro-inflammatory cytokines expression was measured by qPCR. <bold>Results:</bold> TGFβ induced collagen and HSP47 expression in A549 cells. Treatment with T03 attenuated this expression significantly more than pirfenidone in A549. The reduction of collagen was confirmed in HPF. Furthermore, T03 decreased IL6 and CXCL8 expression. <bold>Conclusion:</bold> T03 reduced fibrosis markers with higher efficacy compared to a current standard of care, Pirfenidone. Therefore, we could show that T03 has anti-fibrotic and anti-inflammatory actions relevant to IPF.